Comparable degrees of accelerated cell proliferation will be produced in the epithelium of oral mucosa of the rat by three experimental procedures: dietary zinc deficiency, topical friction and systemic excess of Vitamin A. Concomitant changes in epithelial differentiation will be quantitated and compared in relation to hyperplasia of cellular and keratin layer; cell hypertrophy as reflected in protein synthetic machinery, energy provision and products of synthetic activity; failing disintegrative performance as seen in parakeratosis and retention of cytoplasmic organelles in the keratin layer; deviations in kind from differentiation in controls; and quantitative changes in microcirculation and number of mast cells in the lamina propria. To gain some insight into the cellular processes involved in the paradoxical hyperproliferative and hypertrophic response to zinc deficiency by rat buccal epithelium, we propose to determine the concentration of zinc in bucccal epithelium in experimental and control animals; to determine the intracellular localization of zinc by analysis of subcellular fractions for 65Zn; and to determine the effect of extracts of buccal cells maintained in a zinc-deficient medium on mitotic activity of cells maintained in a zinc-sufficient medium.